State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Genome Biol. 2023 Apr 30;24(1):98. doi: 10.1186/s13059-023-02938-5.
Caloric restriction (CR) has been known to promote health by reprogramming metabolism, yet little is known about how the epigenome and microbiome respond during metabolic adaptation to CR.
We investigate chromatin modifications, gene expression, as well as alterations in microbiota in a CR mouse model. Collectively, short-term CR leads to altered gut microbial diversity and bile acid metabolism, improving energy expenditure. CR remodels the hepatic enhancer landscape at genomic loci that are enriched for binding sites for signal-responsive transcription factors, including HNF4α. These alterations reflect a dramatic reprogramming of the liver transcriptional network, including genes involved in bile acid metabolism. Transferring CR gut microbiota into mice fed with an obesogenic diet recapitulates the features of CR-related bile acid metabolism along with attenuated fatty liver.
These findings suggest that CR-induced microbiota shapes the hepatic epigenome followed by altered expression of genes responsible for bile acid metabolism.
热量限制（CR）通过重编程代谢来促进健康，但对于代谢适应 CR 过程中表观基因组和微生物组如何响应知之甚少。
我们在 CR 小鼠模型中研究了染色质修饰、基因表达以及微生物组的变化。总的来说，短期 CR 导致肠道微生物多样性和胆汁酸代谢改变，从而提高能量消耗。CR 重塑了富含信号反应转录因子（包括 HNF4α）结合位点的基因组位置的肝增强子景观。这些改变反映了肝脏转录网络的显著重编程，包括参与胆汁酸代谢的基因。将 CR 肠道微生物群转移到喂食致肥胖饮食的小鼠中，可重现与减轻脂肪肝相关的 CR 相关胆汁酸代谢特征。
这些发现表明，CR 诱导的微生物群塑造了肝脏表观基因组，随后改变了负责胆汁酸代谢的基因的表达。
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